Pheromone compositions and uses thereof

ABSTRACT

The present invention relates to a composition of less than or equal to about 1% of pheromones useful to treat or prevent a behavioral stress problem of a non-human mammal. It also relates to a device comprising said composition and to a method for preventing and/or treating stress-related behaviors in a non-human mammal, by using said composition or device.

The present invention relates to a composition of pheromones useful totreat or prevent a behavioral stress problem of a non-human mammal. Italso relates to a device comprising said composition and to a method forpreventing and/or treating stress-related behaviors in a non-humanmammal, by using said composition or device.

BACKGROUND OF THE INVENTION

Pheromone therapy, “pheromonatherapy”, or “pheromonotherapy” is a way tomanage behavior problems in non-human mammals by using chemicals thathave pheromonal properties. It is an innovative treatment of stressrelated problems for non-human mammals, such as non-companion animalspecies, including pigs and poultry, or domestic animal species, such ascats and dogs. The pheromonatherapy has been studied most extensively indogs and cats.

Pheromones are chemical substances used for communication betweenindividuals of the same species. Some chemicals that provideinterspecies communication are called allelochemicals. Some compoundsare known to be a pheromone in one species, but have been observed tohave behavioral effects in other species. Pheromones will be used hereinin a large sense, i.e. any naturally or non-naturally occurring compoundthat have a behavioral impact on non-human mammals. The precisemechanism of action of most pheromones is still unknown but they inducesome modifications in both the limbic system and the hypothalamus.

Pheromonotherapy is a great way of managing non-human mammals welfareand more particularly some common stress-related behavioral disorders indomestic mammals, such as dogs and cats, without the need for drugs andtheir associated side-effects.

Pheromonotherapy is successfully used to prevent and/or treat at leastone medical or behavioral stress problem of a non-human mammal for petsand especially for cats and dogs.

For cats, Feliway® (Ceva Santé Animale) was the first synthetic versionof naturally occurring feline facial pheromones and the firstpheromonotherapy used for cat to prevent and/or treat at least onemedical or behavioral stress problem. The product mimics the feline'sfacial pheromones and can be used to calm the pet in stressfulsituations. When sprayed onto objects in the cat's environment, Feliway®decreases the cat's arousal and stops urine marking and verticalscratching, and other stress-related behaviours. The user always needsto wait for about 15 minutes before letting the cat near any Feliway®sprayed areas, in particular as to let the volatile carrier solventevaporate.

As this spray schedule may be challenging to comply with, convenientplug-in

Feliway® devices have been developed and commercialized by Ceva SantéAnimale. These plug-in offer a no-hassle way for pet owners to calmtheir cats. The pet owner has just to attach the Feliway® source to theplug-in diffuser, plug it into an electric socket in the room most usedby the cat, and continue use for four weeks with a liquid plug indiffuser to ensure no relapse in marking behavior.

For dogs, dog appeasing pheromone (DAP® or Adaptil®; Ceva Sante Animale)is a synthetic analog of natural dog-appeasing pheromone that has beenpromoted as an adjunct treatment to improve conditions such asseparation-related behavior problems, loud noise phobias, stress andanxiety. Dog-appeasing pheromone has been reported to reduceseparation-induced anxiety, fear in puppies in a new environment andanxiety and stress during transportation. It can also decrease thestress of dogs in public shelter, the training-derived stress of workingdogs (police dogs, guide dogs) and the anxiety of puppies in learningand socialization processes. Also, Adaptil® might be a potentialtreatment for dogs that are fearful of fireworks. Use of Adaptil® inveterinary clinics was significantly associated with greater relaxationin dogs, but did not have an effect on aggression.

Adaptil® is available in two main forms: spray and plug in diffuser.

Adaptil® spray must be sprayed 15 minutes before the dog is introducedinto the environment (car, carrier, kennel, etc.), in particular to getthe volatile carrier solvent evaporated. Effects should lastapproximately 4-5 hours and repeated applications can be necessary ifthe dog owner notice a reduced effect. It is recommended not to sprayAdaptil® directly on animals nor near an animal's face. Adaptil®diffuser can be plugged into an electric socket in a room, frequentlyused by the dog, and continually used for four weeks with a liquid plugin diffuser to comfort both puppies and adult dogs.

Recently, Ceva Santé Animale has introduced Feliway MultiCat® a felineappeasing pheromone to reduce social tension and conflict between catsliving in the same home. Feliway MultiCat® pheromone is a synthetic copyof the pheromone produced by a mother cat during lactation. Thisappeasing pheromone reassures their kittens and helps them bond with themother. Social tension between cats may impair the cat's day to daywelfare. Conflict between cats can begin when a new cat is introducedinto the home or previously amicable relationships may change when anevent happens that causes one or more cats to become distressed. Thecats may have an aggressive encounter and then fail to mend theirrelationship. Signs of social tension and conflict between familiar catsmay be obvious or quite subtle. Overt aggression may include hissing,growling, screaming, hissing, swatting, or chasing. Passive or avoidantbehaviors are common too including hiding, fleeing or blocking. MeridianAnimal Health Company launched Nutricalm 24/7 Pheromone Collars for catsand dogs to provide round-the-clock pheromone release. The pheromones inthe collars mimic those puppies and kittens are exposed to while nursingand create feelings of security and well-being, even in adulthood.

Perrigo company launched the Sentry® Good Behavior™ pheromone productsto reduce and eliminate problems like inappropriate marking, scratching,digging and even pet/owner separation.

Virbac company launched in 2015 a product branded Zenifel® comprising aF3 feline's facial pheromone analogue which can be used to calm the catin stressful situations. This product contains 10% of pheromone fractionof the total weight for the spray composition and 2% for the plug-indevice.

All pheromone products currently available to treat or prevent behaviorproblems in non-human mammals such as dogs and cats are characterized bya pheromonal fraction around 2 to 10% of the total weight of saidcomposition.

However the prior art does not provide so far an efficient compositioncomprising pheromones with a low amount thereof. There is a need todevelop compositions comprising pheromones at a low amount suitable in avariety of supports and/or useful in a variety of situations, and stilleffective.

SUMMARY OF THE INVENTION

This present invention relates to a composition comprising pheromones inan amount of less than about 1% by weight with respect to the totalweight of said composition.

The composition according to the invention is suitable for a use totreat at least one behavioral stress problem of a non-human mammal, inparticular by administration of the composition to said mammal.

Another object of the present invention is a device comprising acomposition of the invention, the device being more specificallysuitable for a use to treat at least one behavioral stress problem of anon-human mammal.

It also relates to a device comprising said composition and to a methodfor the treatment of a stress-related behavior in a non-human mammal, byusing said composition or device.

DETAILED DESCRIPTION

Definitions:

The term «pheromone » as used herein refers to any compound that mimicscertain naturally occurring pheromones that have a behavioral impact,such as a calming or appeasing effect, on mammals. It includes anynaturally occurring pheromones, said naturally occurring pheromones areone or more secreted compounds by an organism of a specific specieswhich entails a foreseeable reaction (such as for example a calmingeffect) to another mammal of the same species or another species. Asspecified earlier, pheromones will be used herein in a large sense, i.e.any naturally or non-naturally occurring compound that have a behavioralimpact on non-human mammals. The precise mechanism of action of mostpheromones is still unknown but they induce some modifications in boththe limbic system and the hypothalamus.

As used herein, the term “about” or “approximately” or “around” will beunderstood by a person of ordinary skill in the art and will vary tosome extent on the context in which it is used. If there are uses of theterm which are not clear to persons of ordinary skill in the art giventhe context in which it is used, “about” will mean up to plus or minus15% of the particular term.

The percentages are herein expressed by weight, unless otherwisespecified.

“Non-human mammals” is intended to mean all animals with the exceptionof human. The non-human animals include domestic, farm, and zoo animals,including cats, dogs, horses, cattle, tigers, lions, bears, elephants,pigs, boars, etc.. According to the present description, when cats ordogs are cited by way of example, it can be generalized to any otherdomestic, farm, and zoo animals. More specifically, it refers to catsand dogs, and more specifically cats.

According to the invention, the term “comprise(s)” or “comprising” (andother comparable terms, e.g., “containing,” and “including”) is“open-ended” and can be generally interpreted such that all of thespecifically mentioned features and any optional, additional andunspecified features are included. According to specific embodiments, itcan also be interpreted as the phrase “consisting essentially of” wherethe specified features and any optional, additional and unspecifiedfeatures that do not materially affect the basic and novelcharacteristic(s) of the claimed invention are included or the phrase“consisting of” where only the specified features are included, unlessotherwise stated.

The term “object” or “objects” means any physical thing that can be seenand touched. Examples of objects includes any object that a feline mayscratch including, but not limited to, rugs, furniture, carpets, drapes,upholstered corners of couches and chairs, wall papered surfaces,cardboard storage boxes, wood trim on doors and walls. These are only avery few examples defined to encompass the term objects that is usedherein. Moreover, feline including cats, may use or uses at least onespecific object for scratching (i.e. scratching object), such as catposts, cat platforms, cat carpets, cat boards, cat toys, cat trees, andthe like.

The term « fatty acid », according to the invention, refers tomonocarboxylic and dicarboxylic acids with hydrocarbon chains, saturatedor unsaturated, linear or branched, liable to have a behavioral impacton stress of non-human mammals. “Derivatives of fatty acids” means allactive derivatives of fatty acids. Preferably, the derivatives are inester (such as methyl ester) or salt forms.

The composition of the invention comprises pheromones in an amount ofless or equals to about 1% by weight with respect to the total weight ofsaid composition.

According to a particular embodiment of the invention, pheromonescorrespond to at least one fatty acid or derivative thereof, morespecifically salt or ester thereof, such as methyl ester.

The present invention relates to a composition comprising one or morepheromones, preferably one or more fatty acids or derivatives thereof,as active ingredients, in an amount of less or equal to about 1% byweight with respect to the total weight of said composition, preferablyless or equal to about 0.9, 0.8, 0.7, 0.6, or 0.5% by weight withrespect to the total weight of said composition. According to aparticular embodiment, the composition comprises one or more pheromones,preferably one or more fatty acids or derivatives thereof, as activeingredients, in an amount more than or equal to about 0.3% or 0.4% byweight with respect to the total weight of said composition.

The fatty acids preferably have from 3 to 22 carbon atoms. They can beselected for instance from propanoic acid (propionic), butanoic acid(butyric), pentanoic acid (valeric), hexanoic acid (caproic), heptanoicacid (enanthic), octanoic acid (caprylic), nonanoic acid, decanoic acid(capric), undecanoic acid (undecylic), dodecanoic acid (lauric),tridecanoic acid (tridecylic), pentadecanoic acid, heptadecanoic acid(margaric), octadecanoic acid (stearic), eicosanoic acid (arachidic),arachidonic acid, heneicosanoic acid (heneicosylic), tricosanoic(tricosylic), tetracosanoic acid (lignoceric), pentacosanoic acid(pentacosylic), hexacosanoic acid (cerotic), heptacosanoic acid(heptacosylic), octacosanoic acid (montanic), nonacosanoic acid(nonacosylic), triacontanoic acid (melissic), henatriacontanoic acid(henatriacontylic), dotriacontanoic acid (lacceroic), tritriacontanoicacid (psyllic), tetratriacontanoic acid (geddic), pentatriacontanoicacid (ceroplastic), hexatriacontanoic acid (hexatriacontylic),nonanedioic acid (azelaic), oleic acid, y-linoleic acid, palmitic acid,palmitoleic acid, linoleic acid, n-butyric acid, isobutyric acid,[alpha]-methylbutyric acid, tetradecanoic acid (myristic), pentadecylicacid (n-pentadecanoic), heptanedioic acid (pimelic), salt or esterthereof, and a mixture thereof.

According to a specific embodiment, they are chosen among oleic acid,palmitic acid, azelaic acid, pimelic acid, capric acid, myristic acid,palmitoleic acid, linoleic acid, linolenic acid, stearic acid, valericacid, arachidonic acid, lauric acid, n-butyric acid, isobutyric acid,[alpha]-methylbutyric acid, pivalic acid, linoleic acid, eicosapentanoicacid, pentadecanonic acid, tridecanoic acid, docosahexanoic acid, saltor ester thereof, and a mixture thereof.

The compositions may comprise at least one fatty acid such as oleicacid, linoleic acid, palmitic acid, valeric acid, a derivative thereof,or a mixture thereof.

By way of examples, we can quote fatty acid mixtures, or theirderivatives, ester or methyl ester derivatives, such as:

a mixture of oleic and palmitic acid;a mixture of oleic and n-butyric acid;a mixture of valeric and linoleic acid;a mixture of oleic acid, palmitic acid and linoleic acid;a mixture of oleic acid, palmitic acid, linoleic acid and palmitoleicacid;a mixture of capric acid, lauric acid, myristic acid, palmitoleic acid,palmitic acid, linoleic acid and oleic acid;a mixture of oleic acid, palmitic acid, linoleic acid, myristic acid;a mixture of oleic acid, palmitic acid, linoleic acid, lauric acid andmyristic acida mixture of oleic acid, palmitic acid, linoleic acid, myristic acid andpentadecanonic acid;a mixture of oleic acid, palmitic acid, linoleic acid, myristic acid,pentadecanonic acid and stearic acid;a mixture of oleic acid, palmitic acid, linoleic acid, myristic acid,lauric acid and pentadecanonic acid;a mixture of lauric acid, myristic acid, pentadecanonic, palmitic acid,stearic acid, oleic acid, linoleic acid; ora mixture of oleic acid, azelaic acid, pimelic acid and palmitic acid.

According to a particular embodiment, the composition comprises valericacid and linoleic acid (or derivative thereof), as pheromones, in anamount of less than or equal to about 1% by weight with respect to thetotal weight of said composition, preferably less or equal to about 0.9,0.8, 0.7, 0.6, or 0.5% by weight with respect to the total weight ofsaid composition. Preferably, the amount of valeric acid and linoleicacid (or derivative thereof), as pheromones, is more than or equal toabout 0.3% or 0.4% by weight with respect to the total weight of saidcomposition.

The mixture may comprise the above-mentioned fatty acids in appropriateproportions which are well known to any skilled person. By way ofexample, the mixtures can contain (% are expressed by weight withrespect to the total weight of the cited compounds):

about 55-65% of oleic acid and 45-35% of palmitic acid, theirderivatives, salts or esters (e.g., methyl ester) derivatives thereof;

about 45% of oleic acid, 16% of azelaic acid, 18% of pimelic acid, and21% of palmitic acid, their derivatives salts or esters (e.g., methylester) derivatives thereof;about 30% of palmitic acid, 30% of oleic acid, and 40% linoleic acid,their derivatives, salts or esters (e.g., methyl ester) derivativesthereof; orabout 30% of palmitic acid, 40% of linoleic acid, 10% acid palmitoleicand 20% of oleic acid, their derivatives salts or esters (e.g., methylester) derivatives thereof; orabout 30% of oleic acid, 20% of palmitic acid, 20% of linoleic acid, 10%stearic acid, 5% pentadecanoic acid, 5% myristic acid and 2% lauricacid, their derivatives, salts or esters (e.g., methyl ester)derivatives thereof;about 10% of valeric acid and 90% of linoleic acid, their derivatives,salts or esters (e.g., methyl ester) derivatives thereof.

According to an embodiment of the present invention, the pheromones usedherein are compounds to treat or prevent a behavioral stress problem ofa non-human mammal, more particularly either cats or dogs, preferablycats.

According to a particular embodiment of the present invention, the fattyacid mixture comprises a mixture of appeasing fatty acids for cats.Preferably, this mixture comprises at least a therapeutically effectiveamount of active fatty acids, derivatives thereof, salt or ester thereofand preferably chosen among lauric acid, myristic acid, stearic acid,linoleic acid, oleic acid, valeric acid, azelaic acid, pimelic acid,palmitic acid, and a mixture thereof. The mixture of fatty acidspreferably comprises linoleic acid and valeric acid.

According to another embodiment of the invention, the mixture comprisesa mixture of fatty acids that are appeasing for dogs. Preferably, thismixture comprises a therapeutically effective amount of fatty acids,their derivatives, salt or ester thereof. These are preferably chosenamong lauric acid, myristic acid, pentadecanoic acid, palmitic acid,stearic acid, oleic acid and linoleic acid. By way of example, a mixtureof ester fatty acids for dogs comprises about 35% of methyl oleate,about 2% of methyl laurate, about 13% methyl stearate, about 21% methyllinoleate, about 5% methyl myristate, about 4% methyl pentadecanoate,and about 20% methyl palmitate.

According to a preferred embodiment, the composition further compriseslactic acid or an ester thereof, such as methyl or ethyl lactacte.

In a more preferred embodiment, the composition further comprises ethyllactate. According to a specific embodiment, the composition comprisesvaleric acid, linoleic acid and ethyl lactate. Ethyl lactate ispreferred since it seems less degraded during storage than its acidform. The mixture of valeric acid, linoleic acid and ethyl lactate is inappropriate proportions which are preferably about 75-85% of linoleicacid, 5-15% of valeric acid, and 10-20% of ethyl lactate (% areexpressed by weight with respect to the total weight of the citedcompounds).

The composition of the invention can be formulated in any form such as apowder, spray, liquid, gel or aerosol, having components known to thoseskilled in the art. In a particular embodiment, the composition furthercomprises an acceptable carrier. Said acceptable carrier includescompounds well known to one of skill in the art and comprises excipientsand auxiliaries which facilitate processing of the pheromones intopreparations which can be used for non-human mammals. Further details ontechniques for formulation and administration may be found in the latestedition of “Development and Formulation of Veterinary Dosage Forms”edited by Gregory E. Hardee and J. Desmond Baggot (1998)

Generally, the pheromone based composition is in a solution form (fromoily to liquid phases). The composition of the present inventionpreferably comprises at least one solvent.

The solvent includes glycols, such as propylene glycol, diethyleneglycol, glycol ethers (e.g., mono- or di-alkyl ethers of ethyleneglycol), such as ethylene glycol monomethyl ether, ethylene glycolmonoethyl ether, ethylene glycol monopropyl ether, ethylene glycolmonoisopropyl ether, ethylene glycol monobutyl ether, ethylene glycolmonophenyl ether, ethylene glycol monobenzyl ether, diethylene glycolmonomethyl ether, diethylene glycol monoethyl ether, diethylene glycolmono-n-butyl ether, ethylene glycol dimethyl ether, ethylene glycoldiethyl ether, ethylene glycol dibutyl ether, and the like. The solventsmay also be selected from alcohol (such as ethyl alcohol, propylalcohol, isopropanol, 2-propanol,), ether, chloroform, benzene, acetone,volatile oils and the like.

More generally, the active ingredients may be combined with any solid orliquid additives corresponding to the usual techniques of formulationdevelopment. The composition, for instance, may also comprise at leastone volatile organic compound, including, but not limited to, ketones,such as acetone, alcohols, sterols and the like. The composition mayalso comprise coloring agents. The composition may also comprise atleast one antioxidant. Examples of antioxidants include withoutlimitation, sulfate compounds, L-cysteine, thiodipropionic acid,thiolactic acid, monothioglycerol, propyl galate sodium metabisulfite,sodium formaldehyde, sulfoxylate acetate, butylated hydroxyanisole (BHA)and butylated hydroxytoluene (BHT), vitamin E, ascorbic acid (vitaminC), vitamin B12, or a combination of these agents. The antioxidants,such as BHT, may be present in the composition described herein in anamount of 0.001% to 0.1% by weight with respect to the total weight ofsaid composition. The antioxidants, such as BHT, can also be present inthe amount of 0.005% to 0.015% by weight with respect to the totalweight of said composition, preferably 0.01%.

Cat attractants can also be optionally added to the composition. Theseinclude catnip (Nepeta Cataria), essential oil of catnip, tatarianhoneysuckle (Lonicera tartarica), Valerian (Valerriana officicinalis),silver vine/matatabi (Actinidia polygama), cat thyme (Teucrium maxum),Buckbean (Menyanthes trifoliate), actinidine, actinidiolide,boschnialactone, boschniakine, dihydroactinidiolide,dihydronepetalactone, epinepetalactone, iridomyrmecin,isodihydronepetalactone, missugashiwalactone, neonepetalactone,onikulactone and mixtures thereof. The cat attractants may be present inthe composition described herein in an amount of 0.02% to 0.20%,preferably 0.05% to 0.15%, by weight with respect to the total weight ofsaid composition. They can also be present in the amount of 0.01% to0.10% by weight with respect to the total weight of said composition,preferably 0.1%.

Additional components may optionally be included such as, but notlimited to, plasticizers, fragrances, coloring agents, preservatives,light stabilizers, and the like.

An object of the invention is a use of the composition as defined hereinto prevent and/or treat of at least one behavioral stress problem of anon-human mammal, in particular by administration of the pheromonesbased composition to said non-human mammal. The administration of thepheromones based composition to a non-human mammal can be made directlyor indirectly.

The composition of pheromones according to the invention can beadministered to a non-human mammal by propelling or applying thecomposition onto, over or nearby the non-human animal or a part thereof.The method of administration of the composition according to theinvention can be implemented in a place where a non-human mammal islocated. The place can be of any kind, such as for example a confinedplace, for instance a car, truck, carrier, small house or kennel. Forcats, the pheromones-based composition can also be applied to anyscratching object in which the cat has or may have a tendency toscratch, such as cat posts, cat platforms, cat carpets, cat boards, cattoys, cat trees, and the like. This can help the cat not to scratchsomewhere else.

According to a particular embodiment, the invention relates to a methodfor preventing a cat from scratching on multiple objects, said methodcomprising placing at least one composition of the invention on ascratching object (i.e.: an object dedicated for scratching).

The administration onto a non-human mammal or a part thereof or theapplication on an object can be carried out by propelling, spraying,applying or diffusion of the composition of pheromones depending on theforms (solution, solid...) of the composition.

The amount of pheromones to be administered according to the inventionvaries and depends for instance on the nature of pheromones and thenon-human mammal but it should be sufficient to prevent and/or treatbehavioral stress problems of a non-human mammal. In a specificembodiment, the effect should be obtained immediately, e.g. within lessthan 10 minutes, more preferably less than 5 minutes. The administrationcan be renewed, one, two or three times, if no satisfactory effect isobtained or if reduced effect is observed.

The composition of pheromones as defined above is particularly effectiveto prevent and/or treat at least one behavioral stress problem of anon-human mammal.

More particularly, the composition of pheromones according to thepresent invention can prevent territorial urinary marking and/orfamiliarize the animals with a new environment, and/or prevent noisyoutbursts, soiling, destructions, scratching, stamping in theterritories or aggressiveness.

The administration of the composition of pheromones may take place oververy short periods of time, such as for example during travelingperiods, or, on the contrary, can be repeated whenever necessarydepending on the animal behavior. It can be renewed if necessaryaccording to stress behaviors of the non-human mammals.

According to a particular embodiment, the administration or applicationis repeated once a day for two or more days, such as 3, 4, 5, 6, 7, or 8days, then the frequency of administration can be diminished, such asonce weekly for one, two, three or four more applications, to achievebehavioural changes (as to manage for instance cat's scratchingbehaviours).

The composition according to the present invention is particularlyefficient on canine and feline and more especially on dogs and cats.

Behavior stress origins for dogs today could be found for example in theowners' hectic lifestyles difficult to cope with, because owners areconstantly on the go whether it be moving house, going on holiday,having parties and even loud noises people make for fun like fireworksnight. Accordingly, behavior stress signs increases such as for exampleexcessive barking, agitation, trembling, shaking, shivering,drooling/salivating, cowering and hiding, licking, scratching, yawning,clinging to owners, trying to run away/attempting to escape, soiling theplace, excessive pacing and panting, refusing to eat, vomiting, whining,urinating/defaecating, or any combination of said signs.

Cats, unlike dogs, are considered to be territorial animals. They havevery specific behaviors centralized around their territory. Only whentheir environment is secure will some cats develop a relationship withother pets or humans. Stress origins for cats can be for examplemulti-cat households, visiting the vets, moving home, new housefurniture and redecorating, cat carrier . . . The behavior stress signsin cats can be illustrated for example by scratching, urine marking,aggression, food intake disorders (over-feeding), overgrooming (baldareas) or undergrooming (matted or soiled fur), house soiling, decreasedlevels of activity, appearing withdrawn (reduced desire to play orinteract to owners), or any combination of said signs.

The compositions, mixtures, uses and methods according to the presentinvention thus allow preventing and/or treating at least one behavioralstress problem of a non-human mammal. For example, repetitive urinarymarkings of cats occurring in case of stress of cats due tocircumstances or particular changes to their immediate environment. Italso allows the improvement of the conditions for the non-human mammalsto familiarize themselves with their new environment, especially duringtravels, and/or to prevent stamping and territorial destructions, and/orreduce noisy outbursts. The compositions, and mixtures according to thepresent invention are thus intended to be used in circumstances where,for instance, a dog or a cat has shown, or is anticipated to show, signsof stress when being transported in a car.

For cats, the beneficial effects can be measured for example by thereduction of the urinary markings and by the repeated physical contactor rubbing against new objects and people that surround them. Accordingto a specific embodiment, the composition of pheromones according to thepresent invention when applied on a scratching object allows orientationor reorientation of the cats to said object, and consequently prevents acat from scratching on multiple objects. On the whole, the compositionof pheromones according to the present invention allows the improvementof behavior of the non-human mammals in their environment and peoplepresent in that environment, with a notable reduction of stress, urinarymarking and/or noisy outbursts, as well as behavior that is nonaggressive and more relaxed and more affectionate, especially with theirowners.

The composition of pheromones according to the invention may beadministered by any means or devices suitable for administration,preferably in ambient temperature, of said composition to a non-humanmammal or a part thereof or to any object that a non-human mammal has ormay have the habit to touch or scratch.

The present invention also deals with a device comprising a compositionof the invention, preferably the device presents means for the releaseof the composition of pheromones. The device may also comprise means toapply, propel, diffuse or spray the said composition.

In ambient air the composition of pheromones preferably presents itselfunder a liquid or a gel form.

The said device may be, for example, a container, such as a bottle, witha spraying means. A kit comprising a device may also be envisaged, thesaid kit comprising a device, in particular at least one container or anumber of containers, such as vials, a composition as defined in thepresent invention, and optionally a booklet giving instructions to usesaid device. The said device may be in ready-to-use form, i.e.prefilled, or may need to be filled before use.

An object of the invention is a use of the composition or kit as definedherein to treat or prevent a behavioral stress problem of a non-humanmammal.

According to a specific embodiment, the kit comprises at least one vialcomprising the composition of the invention and optionally a bookletgiving instructions to use said at least one vial.

The device or kit according to the invention is suitable for a use toprevent and/or treat of at least one behavioral stress problem of anon-human mammal, in particular by administration of thepheromones-based composition comprised therein to said non-human mammalor by application of the pheromones-based composition comprised thereinon an object, as detailed above.

The present invention will be better understood in view of the Examplesbelow.

EXAMPLES Formulas

Formulas of the compositions according to the invention are detailed inTable 1 below. They were prepared by mixing of the ingredients.

TABLE 1 Compounds Formula A (g) Formula B (g) Valeric acid 0.0425 0.0425Ethyl lactate 0.0625 0.0625 Linoleic acid 0.395 0.395 Coloring agent(black E151) 0.0200 0.0200 Catnip oil 0.1000 0 Valeriana 0 0.1000BHT/BHA 0.0300 0.0300 Propylene glycol qsp 100 qsp 100100 g of formula A corresponds to 96 mL.

Stability Tests

Stability of Formula A was tested over a 7 month-period in a white glassflask and carried out under two controlled temperature and humidityconditions (40° C. and 75% Relative Humidity (RH) or 25° C. and 60% RH).Detection and measures of the valeric acid, ethyl lactate and linoleicacid were made by using Gas chromatography (GC).

Methods: 1. Standard Solution

Approximately 490 mg of linoleic acid, 53 mg of valeric acid and 78 mgof ethyl lactate accurately weighed are introduced into a 50 mlvolumetric flask. This is completed to volume with ethyl acetate. Thesolution is stirred for at least 10 minutes. A dilution 1/20 is made andcompleted to volume with ethyl acetate and the solution is stirred tohomogenize.

2. Sample Preparation:

Approximately 2.5 g of Formula tested is introduced into a 20 mlvolumetric flask. This is completed to volume with ethyl acetate. Thesolution is stirred for at least 10 minutes and filtered through 0.45 gmfilter. The solution is limpid.

3. Chromatographic Parameters:

Gas chromatography equipped with a Capillary Column HP-FFAP 25 m×320 μmand a FID detector at 250° C. 1 μl of the solution is injected in theinlet (250° C.) and eluted through the column with Helium at constantflow (3 ml/min).

Results:

Valeric acid (≈5.2 min), linoleic acid (≈13.5 min) and ethyl lactate(≈2.7 min) are quantified and contents thereof (% w/w) are given by theratio of the areas of the peak corresponding to valeric acid, linoleicacid or ethyl lactate in the chromatogram obtained with the samplepreparation and the standard solution.

Results at 3 and 7 months are given in Table 2.

TABLE 2 T0 month T3 months T3 months T7 months Compounds (% w/w) (40/75)(25/60) (25/60) Valeric acid 0.0425 0.038 0.039 0.039 Ethyl lactate0.0625 0.059 0.060 0.059 Linoleic acid 0.395 0.364 0.386 0.398 Total ofthe fraction 0.425-0.575 0.461 0.485 0.496Formula A is stable and is in compliance with the target concentrationspecifications (±15%).

Efficiency Tests

A trial was made to assess the efficacy of formula A on 173 cats thatwere redirected to new households and on 38 newly adopted cats.Evaluation was made on the efficacy of formula A inmanaging/moderating/preventing undesired vertical cat scratchingbehaviors.

Protocol

The perceived efficacy of the formula A-treated scratch-post wasevaluated over a 4-week period of use.All participants (cats' owners) are male or female, aged 18+, own a cator kitten for which they have full or shared responsibility; and whichis currently healthy (i.e. no major disease, nor undergoing anytreatment), have no more than two cats in their household, have catswhich do not have lesions on the feet, pain in the limbs or back, havecats which are not declawed, have not participated in any research aboutcat scratching in the home, which involved applying a product to ascratch post, have not used any pheromone products within the last 4weeks to manage or prevent cat behavioural problems, have not used anymedications within the last 3 months to manage or prevent catbehavioural problems. All participants in redirected cat households haveexperienced unwanted or troublesome vertical scratching by their cats inhome, such as on fabrics, furniture, carpeted stair-risers, within thelast year. 54% of redirected households currently had at least onescratch post before trial.

All participants in newly adopted cat households did not currently ownscratch post and have a newly adopted cat which had been introduced intotheir household less than 2 weeks before commencing the product trial.

The product is the liquid formula A as defined above. The formula is ina small plastic squeeze tube (5 mL) to be applied in a vertical line ona dedicated scratch post. This process is repeated once a day for 7 daysthen once weekly for 3 more applications. 10 tubes are furnished to theparticipants in a pack. 10 applications were made, one for each of 7consecutive days and three follow-up applications to be used once every7 days until used up (i.e. total usage period of one month).

Results

More than three quarters (about 80%) of cats in redirected householdshad started to use the newly provided scratch post at Day 7.At Day 28, around 9 out of 10 cats in redirected households had used thescratch post (in some capacity) since its introduction into the home.Nearly all (33 out of 38) newly adopted cats had started to use thenewly provided scratch post at Day 7.At Day 28, all newly adopted cats had used the scratch post (in somecapacity) since its introduction into the homeMoreover, 41% of cats in redirected households had started to use thenewly provided scratch post within the first 15 minutes and 74% of newlyadopted cats had started to use the newly provided scratch post withinthe first 15 minutes after first application of the product.

1-14. (canceled)
 15. A composition comprising pheromones in an amount ofless than or equal to about 1% by weight with respect to the totalweight of said composition.
 16. The composition according to claim 15,wherein the pheromones are mixtures of fatty acids selected from: a) amixture of oleic and palmitic acid; b) a mixture of oleic and n-butyricacid; c) a mixture of linoleic acid and valeric acid; d) a mixture ofoleic acid, palmitic acid and linoleic acid; e) a mixture of oleic acid,palmitic acid, linoleic acid and palmitoleic acid; f) a mixture ofcapric acid, lauric acid, myristic acid, palmitoleic acid, palmiticacid, linoleic acid and oleic acid; g) a mixture of oleic acid, palmiticacid, linoleic acid, and myristic acid; h) a mixture of oleic acid,palmitic acid, linoleic acid, lauric acid and myristic acid; i) amixture of oleic acid, palmitic acid, linoleic acid, myristic acid andpentadecanonic acid; j) a mixture of oleic acid, palmitic acid, linoleicacid, myristic acid, pentadecanonic acid and stearic acid; k) a mixtureof oleic acid, palmitic acid, linoleic acid, myristic acid, lauric acidand pentadecanonic acid; l) a mixture of lauric acid, myristic acid,pentadecanonic, palmitic acid, stearic acid, oleic acid, and linoleicacid; and m) a mixture of oleic acid, azelaic acid, pimelic acid andpalmitic acid; said mixtures of fatty acids include mixtures of theirderivatives or esters thereof
 17. The composition according to claim 15,wherein the amount of pheromones is less or equal to about 0.9, 0.8,0.7, 0.6, or 0.5% by weight with respect to the total weight of saidcomposition, and the amount of pheromones is more than or equal to about0.3% or 0.4% by weight with respect to the total weight of saidcomposition.
 18. The composition according to claim 15, wherein thepheromones are mixtures of fatty acids as follows: a) about 55-65% ofoleic acid and 45-35% of palmitic acid, their derivatives, salts orester derivatives thereof; or b) about 45% of oleic acid, 16% of azelaicacid, 18% of pimelic acid, and 21% of palmitic acid, their derivativessalts or ester derivatives thereof; or c) about 30% of palmitic acid,30% of oleic acid, and 40% linoleic acid, their derivatives, salts oresters derivatives thereof; or d) about 30% of palmitic acid, 40% oflinoleic acid, 10% acid palmitoleic and 20% of oleic acid, theirderivatives salts or esters derivatives thereof; or e) about 30% ofoleic acid, 20% of palmitic acid, 20% of linoleic acid, 10% stearicacid, 5% pentadecanoic acid, 5% myristic acid and 2% lauric acid, theirderivatives, salts or ester derivatives thereof; or f) about 10% ofvaleric acid and 90% of linoleic acid, their derivatives, salts oresters derivatives thereof.
 19. The composition according to claim 15,wherein the composition further comprises lactic acid or an esterthereof.
 20. The composition according to claim 15, wherein thecomposition comprises a mixture of valeric acid, linoleic acid and ethyllactate.
 21. The composition according to claim 15, wherein thecomposition comprises a mixture of valeric acid, linoleic acid and ethyllactate and wherein the amounts in said mixture are about 75-85% oflinoleic acid, 5-15% of valeric acid, and 10-20% of ethyl lactate.
 22. Amethod for the treatment of a behavioral stress problem of a non-humanmammal, comprising the administration to said non-human mammal acomposition as defined in claim
 15. 23. The method according to claim22, wherein the composition is administered to a non-human mammal bypropelling or applying the composition onto, over or near the non-humananimal or a part thereof.
 24. The method according to claim 22, whereinthe non-human mammal is a canine or feline.
 25. The method according toclaim 24, wherein the non-human mammal is a dog, and the behavioralstress problem is a stress sign selected from excessive barking,agitation, trembling, shaking, shivering, drooling, salivating, coweringand hiding, licking, scratching, yawning, clinging to owners, trying torun away, attempting to escape, soiling the place, excessive pacing andpanting, refusing to eat, vomiting, whining, urinating, defaecating, andany combination thereof.
 26. The method according to claim 24, whereinthe non-human mammal is a cat, and the behavioral stress problem is astress sign selected from scratching, urine marking, aggression, foodintake disorders, overgrooming or undergrooming, house soiling,decreased levels of activity, appearing withdrawn, or any combination ofsaid signs.
 27. A method for preventing a cat from scratching onmultiple objects, said method comprising placing at least onecomposition according to claim 15 on an object scratched by said cat.28. A device comprising a composition as defined in claim 15, saiddevice comprising a means for the release of the composition ofpheromones.
 29. A kit comprising a device according to claim 28, andoptionally a booklet providing instructions for the use of said device.